Results of standard treatment for squamous cell carcinoma (SCC) of the head and neck or esophagus are poor. New approaches employing combined modality treatment, new combination chemotherapy regimens and new agents are needed. In Project A, newly diagnosed pts with esophageal SCC receive 2 cycles of cisplatinum, bleomycin and VP 16-213 prior to local treatment (surgery or radiotherapy). Those with recurrent disease receive the 3 drug combination until disease progression. To date, among 6 pts there are 2 partial responses (PR), 1 minor response, 1 early death, and 2 are too early to evaluate. In Project B, a combined modality approach is employed for previously untreated, pts with unresectable head and neck SCC. Two cycles of cyclophosphamide and cis-platinum are given prior to radiotherapy and then continued during radiotherapy. One pt has been entered. In Project C, advanced, recurrent head and neck cancer is treated with the combination of cis-platinum and cyclophosphamide. To date, responses in 12 evaluable pts are: 2 CR and 6 PR (66%). Project D evaluates new agents (see also report Z01 CM 09117 03 COB). A phase II trial for recurrent head and neck cancer with aziridinylbenzoquinone (AZQ) has accrued 4 pts.